Summary of Work: Systemic lupus erythematosus (SLE) is an autoimmune disease that can severely damage the kidneys, joints, and other tissues. The role of genetic susceptibility in SLE has been extensively examined, but relatively little is known about the contribution of specific hormonal and environmental influences involved in the etiology of SLE. Our study focuses on measures of endogenous hormone exposure (menstrual and reproductive history), exogenous sources of estrogen (including estrogen replacement therapy, fertility drugs, and environmental estrogens), and occupational exposures that have been linked to the development of SLE or other autoimmune diseases (e.g., silica dust). A population-based case-control study of recently diagnosed patients living in eastern North Carolina and South Carolina underway: 300 cases and 300 controls frequency matched by age, gender, and state will be enrolled. Cases are identified through private-practice rheumatologists, 4 university-based rheumatology practices, public health clinics, and patient support groups. Population-based controls will be identified through driver's license records. A standardized interview includes assessment of previous medical history, family medical history, work and other activities with the potential of exposure to specific materials, and for women, reproductive and menstrual history. Serum will be collected to measure specific autoantibodies. White blood cells will be stored for additional studies of gene- environment interactions relating to metabolism, immune function, and hormones.